EP1673609B1 - Device and method for handling a probe - Google Patents

Description

The invention relates to a device and a method for handling a sample, in particular for processing, examination or storage or removal of a cryoprobe according to the preambles of claims 1 and 12, respectively.

It is known in the field of biology, pharmacology, medicine and biotechnology to freeze samples of biological material while maintaining the vitality of the sample material at liquid nitrogen temperatures. Such samples are also referred to as cryoprobes and are usually stored and transported in sample containers, the sample containers are introduced to freeze the samples in so-called cryogenic tanks, in which there is liquid nitrogen. However, various problems arise during the storage of the sample containers in the cryotanks and in the later removal of the sample containers from the cryotanks, which are briefly described below.

On the one hand, the cryotanks must be opened for storage or removal of the sample container with the cryoprobes therein, whereby moisture from the air surrounding the cryotank can enter the cryotank, which leads to ice formation in the cryotank.

On the other hand, the sample containers removed from the cryotank, as they are removed from the cryotank, come into contact with the relatively warm and moist air surrounding the cryotank, which leads to condensations and subsequent ice formation on the sample containers removed. This ice formation is undesirable because it makes it difficult to identify the sample containers and automate the handling processes and requires defrosting, abrading or otherwise removing the frost or icing formed on the sample container. In addition, ice formation on the sample containers may also make electrical contacts on the sample containers inaccessible and freeze movable mechanical devices on the sample containers.

In addition, the contact of the cryoprobes with the germ-containing ambient air can lead to contamination, which is also undesirable.

However, the problems described above not only occur in the storage and retrieval of sample containers in cryotanks, but also in other handling or processing of sample containers with cryoprobes, when they come into contact with the surrounding air.

Out US-A-4,680,945 is a device or a method according to the preamble of the independent claims known. However, bacteria, viruses and other particles can also outgas from the liquefied protective gas. Furthermore, it should be noted on the prior art FR 772 020 A and US-A-3,267,830 ,

The invention is therefore based on the object to prevent in a generic device or a generic method that outgas from the liquefied inert gas, viruses and other particles.

This object is achieved by a device according to claim 1 and a method according to claim 12.

The invention includes the general technical teaching, in the handling of samples or sample containers to prevent contact with the surrounding relatively humid, usually germ-containing air, so that no ice formation on the samples or sample containers can occur and do not germinate the samples.

In the context of this general inventive idea, the formation of ice on the sample containers or samples and their microbial contamination can be prevented in various ways, as will be explained below.

One possibility for this is to surround the samples or sample containers with a protective gas during handling in order to prevent direct contact with the relatively moist ambient air. The protective gas is preferably gaseous nitrogen, which is used in any case for cooling the cryoprobes and can therefore also be used as a protective gas for the samples or sample containers without much additional effort. However, the invention is not limited to nitrogen with respect to the protective gas to be used, but in principle also with other protective gases can be realized, which prevent ice formation on the samples or sample containers.

Another possibility for preventing ice formation on the samples or sample containers is to cool the ambient gas surrounding the samples or sample containers, in order to reduce the temperature gradient between the ambient gas and the surface of the samples or sample containers and thereby cause condensation on the samples or sample containers To counteract sample containers.

Furthermore, it is possible to dry the ambient gas surrounding the sample or sample containers in order to prevent ice formation on the samples or sample containers.

However, the techniques for preventing ice formation described above are not mutually exclusive but may be used in any combination with each other.

The protective gas can therefore fulfill various functions within the scope of the invention, namely cooling, drying and protection against microbial contamination.

For drying, cooling and / or for exchanging the ambient gas surrounding the sample or the sample container, the device according to the invention has an air-conditioning device, the term of an air-conditioning device used in the context of the invention generally being to be understood. For example, the function of the air conditioning device can also be fulfilled by liquid nitrogen, which is contained in a cryotank serving for storing the samples and at least partially replaces the ambient gas of the sample or of the sample container and thereby protects the sample or the sample container. In this case, the air conditioning device consists of the components that allow outgassing of the liquid nitrogen from the cryotank into the environment of the sample or the sample container.

According to the invention, a protective container is provided which receives the sample or the sample container during handling, wherein the air conditioning device is connected to the protective container to dry the ambient gas in the protective container to cool and / or by the inert gas replace. In the protective container, an artificial atmosphere is thus created, which prevents ice formation on the sample or the sample container.

The protective container may be formed, for example, as a protective bell or protective cover, wherein the protective hood or protective bell preferably has on its underside an opening to introduce the sample or the sample container or to be taken. Such a protective hood or protective bell can be placed on the sample or the sample container in order to protect it in a subsequent handling. However, it is also possible that the protective hood or protective bell is placed on a cryotank, so that the removal opening of the cryotank is within the protective hood or protective bell and thus also protected.

In a variant of the invention, the protective hood or protective bell can be walked on, so that an operator within the protective hood or protective bell can handle the sample or the sample container.

In such a walk-in protective container, it is advantageous if the device according to the invention has a breathing air supply for the operator located in the protective container, which breathing air supply can consist of a breathing air hose in the simplest case, which connects the operator with the outside of the protective container.

In another variant of the invention, however, the protective container is portable, so that even during the transport of a sample or a sample container ice formation can be prevented.

According to the invention, the above-mentioned protective container air conditioning means comprises a source of inert gas for at least partially filling the protective container with the inert gas, the inert gas preventing deterioration of the sample during its handling. Such a protective gas source may comprise, for example, an at least partially open inert gas storage vessel, in which the protective gas is in liquefied form, wherein the liquefied inert gas in the protective container outgassing. For example, there may be liquid nitrogen in the protective gas storage vessel, which outgasses due to the ambient heat in the protective container.

Furthermore, a heating element can be provided which heats the liquefied inert gas in the inert gas storage vessel and thereby promotes and accelerates outgassing. Such a heating element may for example consist of a power heater, but other designs of the heating element are possible.

In addition, the inert gas storage vessel to a filter element to retain the outgassing of the protective gas bacteria, viruses and other particles that are in the liquefied inert gas.

Furthermore, it is advantageous if the protective container has an at least partially transparent container wall in order to allow a visual inspection during the handling of the sample. This can be achieved, for example, in that the container wall is made entirely of glass or a transparent plastic, but it is also possible that only single viewing windows are mounted in the otherwise opaque container wall.

Furthermore, an outlet opening is preferably arranged on the upper side of the protective container, via which excess protective gas can be discharged.

In this case, it is useful if an outlet tube is connected to the outlet opening on the outside of the protective container, which has an outlet opening located outside the protective container and directed downwards. This orientation the mouth opening of the discharge tube advantageously prevents that from the outside air can fall into the protective container.

In a preferred embodiment of the invention, the protective container further comprises a gas-tight or gas exchange-reduced engagement, so that the sample or the sample container located in the protective container can be handled from the outside by an operator.

In addition, the device according to the invention can have a gas-tight or gas-exchange-reduced lock in order to be able to introduce or remove the sample or the sample container or other parts into the protective container.

In a variant of the invention, this lock consists of at least one opening in the protective container and a flexible curtain covering the opening.

Such a design of the lock offers on the one hand the advantage that no separate operating step is required to open and close the lock.

On the other hand, this design of the lock allows a quasi-continuous introduction and removal of parts, which is important, for example, in an automatic operation on a strip line, with cryoprobes being moved from workstation to workstation.

The cold protective gas in the protective container usually leads to a corresponding cooling of the container wall, which can lead to cold-induced condensation on the outside.

In a variant of the invention, the protective container therefore has a heatable container wall in order to prevent such cold-caused condensation on the outside of the container wall. The heating of the container wall can be done for example by blowing, but other heating methods for heating the container wall can be used.

In another variant of the invention, however, the container wall is thermally insulated to reduce the cold-induced condensation on the outside of the container wall. For example, the container wall can be made of Plexiglas for this purpose, wherein the wall thickness is preferably in the range of 8 to 15 mm in order to achieve a sufficient insulation effect.

Furthermore, a UV lamp can be arranged in the protective container in order to sterilize the interior of the protective container.

In addition, it is also possible to arrange a camera in the protective container to monitor the sample or the sample container.

Furthermore, it should be mentioned that the general technical idea described above can also be realized without a protective container. For example, the sample or the sample container can be blown with a protective gas in order to displace the otherwise relatively moist ambient air in the vicinity of the sample or of the sample container. In addition, the sample or the sample container may also be surrounded by a protective gas curtain, which is produced by suitable blowing nozzles.

In the following, a further variant of a cooling device according to the invention will first be described generally.

This cooling device according to the invention has for receiving refrigerated goods to a cooling space, which is bounded by an inner wall and an outer wall, wherein there is a gap between the inner wall and the outer wall, in which a coolant supply line opens. The coolant (eg, liquid nitrogen) is thus not introduced directly into the cooling space, but into the space between the inner wall and the outer wall of the cooling chamber, wherein the inner wall is permeable to the coolant, so that the coolant from the space between the outer wall and the inner wall enters through the inner wall into the cooling space.

Preferably, a buffer material is arranged in the intermediate space between the inner wall and the outer wall of the cooling space, which temporarily receives the coolant introduced into the intermediate space and discharges it continuously through the inner wall into the cooling space.

The buffer material is therefore preferably porous, for example, to be able to buffer liquid nitrogen.

The outer wall of the cooling space is preferably impermeable to the coolant, in contrast to the inner wall of the cooling space, in order to prevent leakage of the coolant outwards into the environment. In addition, the outer wall is preferably thermally insulating, in order to avoid a cooling of the environment or a heating of the cooling device.

By contrast, the inner wall of the cooling space preferably consists of a thermally conductive material, such as metal, for the heat transfer from the inner cooling space to improve the coolant in the gap. Moreover, it is advantageous if the material of the inner wall not only has a good thermal conductivity, but also has a high specific heat capacity, so that the inner wall counteracts with its heat capacity as a thermal buffer undesirable temperature fluctuations.

In a preferred embodiment of the invention, the inner wall is substantially grid-shaped, so that the coolant located in the intermediate space can outgas largely unhindered in the refrigerator.

Furthermore, in a preferred embodiment of the invention, the cooling chamber is trough-shaped and has a peripheral edge on its upper side, wherein the coolant supply line preferably has a coolant distributor which extends along the peripheral edge of the cooling space and distributes the coolant over its length into the intermediate space between the cooling space Interior wall and the outer wall of the refrigerator introduces. The coolant is thus introduced evenly into the intermediate space between the inner wall and the outer wall of the cooling space, which advantageously leads to a uniform temperature distribution in the cooling space, since the cooling space is uniformly cooled from all sides.

In addition, there is the possibility within the scope of the invention that a heating element is arranged in the cooling space in order to heat the cooling space or to thaw the refrigerated goods located in the cooling space. Preferably, this heating element is arranged under or in a heating plate, wherein the heating plate preferably has a plurality of passages, which allow gas circulation.

In this case, it is possible to put on the cold room a removable protective bell to prevent the ingress of moisture into the refrigerator. Preferably, this protective bell is at least partially transparent in order to allow a visual inspection of the refrigerated goods located in the refrigerator.

In a preferred embodiment of the invention, the protective bell has a sample lock, through which the goods to be cooled can be introduced into the cooling space or removed from the cooling space, wherein the sample lock largely prevents heat exchange with the environment.

Furthermore, a cold gas outlet can be arranged on the underside of the protective bell and / or on the upper side of the cooling space, via which coolant or cold gas can escape from the cooling space. This cold gas outlet causes a large temperature gradient in the height of the cold gas outlet, wherein the temperature above the cold gas outlet is substantially higher than below the cold gas outlet. In this way, a fogging of the protective bell is advantageously prevented.

Furthermore, in the context of the invention preferably takes place a regulation of the temperature in the refrigerator. For this purpose, the cooling device according to the invention preferably has a temperature sensor arranged in the cooling space in order to measure or regulate the temperature in the cooling space. As an actuator for temperature adjustment then preferably a controllable coolant valve is provided which adjusts the amount of coolant supplied or the coolant flow. The actual temperature control is then performed by a temperature controller, which is connected on the input side to the temperature sensor and the output side controls the coolant valve according to a predetermined temperature setpoint.

The control of the coolant valve by the temperature controller can in this case take place via a clock generator which alternately opens and closes the coolant valve, wherein the opening and closing times of the coolant valve are predetermined by the clock and set by the temperature controller. The coolant is thus supplied discontinuously by the coolant valve opens and closes alternately.

Preferably, the temperature sensor for detecting the temperature in the cooling space is arranged here at the processing position of the cooling space in order to measure or regulate the optimum processing temperature in the cooling space.

The temperature controller therefore preferably regulates the temperature in the cold room so that no coolant lake forms at the bottom of the cold room.

It should also be mentioned that the coolant is preferably liquid nitrogen, but the invention is not limited to nitrogen as a coolant, but can also be realized with other liquid or gaseous coolants which flow into the space between the inner wall and the outer wall the refrigerator can be initiated.

The cooling device according to the invention can be used for various temperature ranges, such as at temperatures of about -150 ° C, -130 ° C, -80 ° C, -40 ° C, + 4 ° C or + 37 ° C, the above-mentioned Temperature ranges may include, for example, a range of ± 10 ° C, ± 5 ° C or ± 2 ° C. A temperature of 37 ° C is advantageous because the growth temperature of biological cells is then optimal. A temperature of + 4 ° C, however, offers the is. On the other hand, a temperature of + 4 ° C offers the advantage that the physiological processes in the cells are slowed down. When cells are manipulated at a temperature of less than 4 ° C, cell damage is lower (eg with tropsia and DMSO).

Finally, the invention encompasses not only the above-described cooling device as a device, but also the use of such a cooling device for the examination, processing and / or manipulation of a cryoprobe.

Figur 1

eine erfindungsgemäße Schutzhaube in perspektivischer Darstellung,

Figur 2

ein alternatives Ausführungsbeispiel einer Schleuse der in Figur 1 gezeigten Schutzhaube in einer Perspektivansicht

Figur 3

ein alternatives Ausführungsbeispiel einer erfindungsgemäßen Vorrichtung mit einem zylindrischen Schutzbehälter,

Figur 4

eine Seitenschnittansicht einer begehbaren Kryotankglocke,

Figur 5

ein nicht erfindungsgemäßes Ausführungsbeispiel einer derartigen Kryotankglocke,

Figur 6

ein einfaches Ausführungsbeispiel einer tragbaren Schutzglocke in einer Seitenansicht,

Figur 7

eine Perspektivansicht eines alternativen Ausführungsbeispiels einer erfindungsgemäßen Vorrichtung,

Figur 8

eine Perspektivansicht eines bevorzugten Ausführungsbeispiels der erfindungsgemäßen Kühleinrichtung mit einer aufgesetzten Schutzglocke,

Figur 9

eine Perspektivansicht der Schutzglocke aus Figur 8 im abgenommenen Zustand,

Figur 10

eine Querschnittsansicht der Wandstruktur des Kühlraums bei der Kühleinrichtung aus Figur 8,

Figur 11

eine vereinfachte perspektivische Darstellung der Kühlmittelzufuhr bei der Kühleinrichtung aus Figur 8 sowie

Figur 12

ein regelungstechnisches Ersatzschaltbild der Kühleinrichtung aus Figur 8.

Other advantageous developments of the invention are characterized in dependent claims or are explained in more detail below together with the description of preferred embodiments of the invention with reference to FIGS. Show it:

FIG. 1

a protective hood according to the invention in a perspective view,

FIG. 2

an alternative embodiment of a lock of in FIG. 1 shown guard in a perspective view

FIG. 3

an alternative embodiment of a device according to the invention with a cylindrical protective container,

FIG. 4

a side sectional view of a walk-in cryotank bell,

FIG. 5

a non-inventive embodiment of such Kryotankglocke,

FIG. 6

a simple embodiment of a portable protective bell in a side view,

FIG. 7

a perspective view of an alternative embodiment of a device according to the invention,

FIG. 8

a perspective view of a preferred embodiment of the cooling device according to the invention with an attached protective bell,

FIG. 9

a perspective view of the protective bell FIG. 8 in the removed condition,

FIG. 10

a cross-sectional view of the wall structure of the cooling space in the cooling device FIG. 8 .

FIG. 11

a simplified perspective view of the coolant supply in the cooling device of Figure 8 and

FIG. 12

a control engineering equivalent circuit diagram of the cooling device FIG. 8 ,

The cross-sectional view in FIG. 1 shows a protective cover 1 made of Plexiglas with a wall thickness of 12 mm and a substantially parabolic cross section, wherein the end faces of the protective cover 1 are closed on both sides by a respective end wall 2.

At the end walls 2, a handle 3 is fixed in the upper area, so that the protective cover 1 can be raised and offset by an operator.

It should also be mentioned that the wall of the protective hood 1 is completely transparent, which allows the operator to visually inspect the interior of the protective hood 1.

On its underside, the protective cover 1 has a circumferential seal 4, which seals the protective cover 1 after it has been placed on a laboratory surface 5.

Furthermore, the guard 1 in the parabolic part of its container wall on two interventions 6, via which the outside operator in the interior of the protective hood 1 can handle.

Furthermore, the protective hood 1 has a gas exchange-reduced lock 7, which is designed as a drawer and is arranged in the end wall 2 of the protective hood 1. On its upper side, the lock 7 has a cover 8, which can be folded up for insertion or removal of a part of the protective hood 1.

On the laboratory surface 5 is located as an air conditioning device a trough 9, which is filled with liquid nitrogen 10. After placing the protective cover 1 on the trough 9, the outgassing of the trough 9 nitrogen fills the interior of the protective hood 1 and serves as a protective gas, as will be described in detail.

In the tub 9 in this case an electric heating element 11 is arranged to heat the in-tub 9 liquid nitrogen 10 and thereby accelerate the outgassing of nitrogen.

Further, an outlet opening is arranged at the top of the protective hood 1, to which a discharge pipe 12 is connected is, can be derived from the interior of the protective hood 1 over the excess nitrogen gas.

The discharge pipe 12 is in this case U-shaped, wherein the free mouth opening of the discharge pipe 12 is directed downward to prevent the collapse of relatively humid ambient air into the interior of the protective hood 1.

The protective cover 1 described above can be placed on a cryoprobe container, not shown for simplicity, wherein the outgassing of nitrogen gas from the trough 9 prevents condensations or even ice formations on the cryoprobe when removing a cryoprobe from the Cryoprobenbehälter.

The perspective view in FIG. 2 shows an alternative embodiment of a lock 7 ', which can be used instead of the lock 7 shown in Figure 1. The lock 7 'is largely consistent with the in FIG. 1 lock shown 7, so that the same reference numerals are used for corresponding components, but which are marked for distinction by an apostrophe.

A special feature of the lock 7 'in comparison to the lock 7 is that it is not designed as a sliding drawer, but is rotatably mounted in the end wall 2'.

This in FIG. 3 illustrated embodiment of a device according to the invention is largely consistent with the in FIG. 1 shown and described above, so that to avoid repetition largely to the above description FIG. 1 is referenced and for corresponding components, the same reference numerals are used, which, however, are distinguished for distinction by two apostrophes.

A special feature of this embodiment is that a cylindrical protective container 1 "is used in place of the parabolic guard 1, wherein the protective container 1" stationary in an insulating pan 13 "is arranged, which thermally insulated the protective container 1".

Furthermore, the protective container 1 "at both end faces in each case a lock for removal or for the introduction of parts, wherein the two locks each consist of an opening in the front side of the protective container 1" and a flexible curtain 14 ", 15", the respective Covering flexible opening and thereby prevents the penetration of relatively humid air from the outside into the protective container 1 ".

Furthermore, in the drawing, only a single engagement 6 "is shown, which opens on the inside of the protective container 1" in a rubber glove 16 ", however, a further engagement is additionally provided, which is not shown for simplicity.

In a lower region of the protective container 1 "is liquefied nitrogen 10", which is heated by a heating element 11 "so that the nitrogen gas in the interior of the protective container 1" outgas.

Above the liquefied nitrogen 10 "there is a working platform 17" with holes for the passage of the nitrogen gas outgassing from below.

In operation, cryoprobe containers containing cryoprobes can be introduced into the interior of the protective container 1 "and manipulated inside the protective container 1" without the risk of condensation or ice formation on the cryoprobe containers.

The cross section drawing in FIG. 4 first shows a conventional cryotank 18 in which liquefied nitrogen 19 is located at the bottom.

In the cryotank 18 a plurality of Cryoprobenbehälter 20 are suspended, which are cooled by the liquefied nitrogen 19 and each containing a large number of cryoprobes.

On its upper side, the cryotank 18 has a tank opening which can be closed by a tank lid 21, wherein the tank lid 21 is shown in the drawing in a raised position in which a Kryoprobenbehälter 22 is removed through the tank opening of the cryotank 18.

With such removal of the Cryoprobenbehälters 22 is traditionally the risk that humidity from the ambient air is incident in the cryogenic tank 18, resulting in the cryotank 18 to undesirable ice formations. In addition, in the conventional sampling methods on the Cryoprobenbehälter 22 condensation and subsequent ice formation occur, which is also undesirable.

To prevent these undesirable effects, the invention comprises a Kryotankglocke 23 which can be raised via a cable 24 and then placed on the tank opening of the cryotank 18, wherein a seal 25, the tank opening of the cryotank 18 seals.

By means of a further cable pull 26, the tank lid 21 of the cryotank 18 can then be lifted by means of two deflection rollers in order to release the tank opening of the cryotank 18 for removal of the cryoprobe container 22.

The removal of the Kryoprobenbehälters 22 then takes place via a further cable 27, which is hooked into a corresponding hook on the Kryoprobenbehälter 22.

The operation of the two cables 26, 27 and the manipulation of the Kryoprobenbehälters 22 takes place here by an operator 28, which can climb over a rollable staircase 29 in the walk-in Kryotankglocke 23 into it.

The operator 28 in this case wears a protective suit and a breathing air supply 30, which is connected via a line 31 with a supply unit arranged outside the cryotank, wherein the supply unit is not shown for the sake of simplicity.

As an alternative to the breathing air supply 30, it is also possible to provide a simple breathing air hose 32 which is guided out of the cryotank bell 23, the free mouth opening of the breathing air hose 32 being angled downwards on the outside of the cryotank bell 23 in order to precipitate moist ambient air into the cryotank bell in any case to prevent.

The air conditioning of the gas volume within the Kryotankglocke 23 takes place here by an electric heating element 33, which is discharged by the operator 28 via a cable into the cryogenic tank 18, so that the heating element 33, the liquefied nitrogen 19 is heated and thereby the Outgassing of nitrogen gas into the interior of the cryotank bell 23 accelerates.

The outgassing nitrogen gas condensations or even ice formation on the removed Kryoprobenbehälter 22 are prevented.

In addition, it is prevented by the Kryotankglocke 23 that upon opening the tank lid 21 moist ambient air falls into the cryogenic tank 18, which would also lead there to an undesirable ice formation.

This in FIG. 5 illustrated embodiment is largely consistent with that described above and in FIG. 4 illustrated embodiment, so to avoid repetition, reference is made largely to the above description and the same reference numerals are used for corresponding components, which are characterized, however, for distinguishing by an apostrophe.

A special feature of this embodiment is that the cryotank bell 23 'is not accessible.

Instead, the cryotank has interventions 34 'through which the operator 28' can manipulate the cryoprobe container 22 'lifted out of the cryotank 18'.

This in FIG. 6 illustrated embodiment of a device according to the invention consists essentially of a protective bell 35, which is connected via a gas line 36 with a nitrogen gas cylinder 37, wherein the gas line 36 opens into the protective bell 35 in a nozzle assembly 38, is discharged through the nitrogen into the interior of the protective bell 35.

In the protective bell 35 are shelves 39 and hooks 40 for holding Kryoprobenbehältern 41. The Cryoprobenbehälter 41 are in this case disposed within the protective bell 35 and are thereby protected by the flowing out of the nozzle assembly 38 nitrogen gas, creating a condensation on the Kryoprobenbehältern 41 or even Ice formation is prevented.

Finally shows FIG. 7 a further embodiment of the invention with a protective container 42 into which cryoprobes or other parts can be introduced or removed via a lock 43.

In this case, nitrogen gas is introduced into the protective container 42 via a gas feed line 44 and directed there to a cryoprobe container 45.

The cryoprobe container 45 can be manipulated by two interventions 46 from the outside by an operator, for which purpose, for example, a pair of pliers 47 can be used.

At the top of the protective container 42 is a controllable valve 48, which initially allows a removal of the relatively humid air in the protective container 42, as long as the protective container 42 is not completely filled with nitrogen gas.

Subsequently, the valve 48 directs the nitrogen gas exiting at the top via a hose 49 to a circulating air system 50, which introduces the nitrogen gas discharged via the valve 48 back into the protective container 42.

Also in this embodiment, the nitrogen gas surrounding the cryoprobe container 45 prevents condensation or even ice formation on the cryoprobe container 45.

That in the Figures 8-12 illustrated embodiment of a cooling device 51 according to the invention is used to control the temperature of a cold room for receiving cryoprobes in an investigation, manipulation and / or processing.

For this purpose, the cooling device 51 a cryogenic sump 52 with a trough-shaped, open-topped cooling chamber 53, wherein on the cryogenic sump 52 a removable protective bell 54 is placed, which prevents the ingress of moisture from the environment into the refrigerator and in detail FIG. 2 is shown.

The protective bell 54 has to introduce the cryoprobes into the cooling chamber 53 and to remove the cryoprobes from the cooling chamber 53 to a sample lock 55 which is mounted laterally on the protective bell 54 and during insertion of the cryoprobes or when removing the cryoprobes heat exchange with the Environment largely prevented and minimizes the moisture in the refrigerator 53.

Furthermore, the protective bell 54 has on its upper side a lamp 56 in order to illuminate the cooling space 53 and thereby facilitate the manipulation of the cryoprobes located in the cooling space 53.

The protective bell 54 itself consists of a transparent material, which allows a simple visual inspection by an operator.

At the beveled front of the protective bell 54 are two conventional glove cuffs 57, 58, through which an operator can manipulate the cryoprobes located in the cooling chamber 53 without gas exchange.

Furthermore, there are two openings 59 at the bottom of the protective bell 54 at the bottom, via which cold gas can escape from the protective bell 54. The two openings 59 have the consequence that sets in the height of the two openings 59, a large temperature gradient, since cold gas escapes from the two openings 59 to the outside. The atmosphere in the protective bell 54 above the openings 59 is therefore much warmer than below the openings 59, which counteracts fogging of the inner walls of the protective bell 54.

At the top of the cryotube 52 is located at the front on a control and display panel 60, where the temperature in the cooling chamber 53 can be displayed and adjusted.

The cooling of the cooling chamber 53 in this case takes place by liquid nitrogen, which is supplied from a nitrogen tank (eg an Apollo tank) via a nitrogen line 61, wherein the nitrogen line 61 does not open directly into the cooling chamber 53rd to the formation of a nitrogen lake at the bottom of the Refrigerator 53 to avoid. Instead, the nitrogen line 61 opens via an electrically controllable coolant valve 62 in a coolant supply line 63, wherein the coolant supply line 63 extends along the peripheral edge of the trough-shaped cooling chamber 53 and indicates the liquid nitrogen distributed over the length.

The cooling space 53 is in this case bounded by a lattice-shaped inner wall 64 which is made of metal and which extends from an outer wall 65 is enclosed, wherein the inner wall 64 and the outer wall 65 include a gap in which a buffer material 66 is arranged. The coolant supply line 63 is arranged in the lateral direction between the inner wall 64 and the outer wall 65 above the buffer material 66 and has downwardly directed outlet openings, is discharged through the liquid nitrogen from the interior of the coolant supply line 63 into the buffer material 66. The buffer material 66 absorbs the liquid nitrogen and discharges it continuously through the grid-shaped inner wall 64 into the cooling space 53.

In this case, the coolant valve 62 operates discontinuously in that the coolant valve 62 either closes or opens.

The control of the coolant valve 62 takes place here by a timer 67, wherein the opening time T _OPEN and the closing time T _ZU are predetermined for the coolant valve 62 by a controller 68 to meter the coolant.

In this case, the regulation takes place as a function of the temperature in the cooling space 3, which is measured by a temperature sensor 69, wherein the temperature sensor 69 is arranged at the processing position of the cooling space 53.

The temperature sensor 69 therefore measures a temperature T _IST and forwards them to a subtractor 70, which receives as a further input variable a setpoint T _SOLL for the temperature in the cooling space 53 and calculates a setpoint-actual deviation ΔT.

The controller 68 then sets the opening time T _AUF and the closing time T _ZU for the coolant valve 62 such that the desired temperature (eg -630 ° C.) in the cooling space 53 prevails, without forming a nitrogen lake at the bottom of the refrigerator 53.

Furthermore, a heating plate 71 is arranged on the bottom of the cooling space 53, which allows heating of the cryoprobe and the cooling space 53.

In the heating plate 71 in this case numerous vertically continuous passages 72 are arranged, which allow gas circulation.

The invention is not limited to the preferred embodiments described above. Rather, a variety of variants and modifications is possible, which also make use of the inventive idea and therefore fall within the scope.

Claims (15)

1. A device for handling a sample, in particular, for treating, examining or inserting or extracting a cryosample, the sample being surrounded during the handling by an ambient gas, with

   - a climate control equipment (9-11, 10", 11'') that cools, dries and/or at least partially replaces the ambient gas with a protective gas in order to avoid a deterioration of the sample by the ambient gas,

   - a protective container (1, 1'') for receiving the sample during the handling, the climate control equipment (9-11, 10'', 11'') being connected to the protective container (1, 1'') in order to dry and cool the ambient gas present in the protective container (1, 1'') and/or replace it with the protective gas

   - a protective gas source (9, 10, 10'') that is part of the climate control equipment (9-11, 10'', 11'') in order to fill the protective container (1, 1'') at least partially with a protective gas, the protective gas preventing a deterioration of the sample during its handling,

   - wherein the protective gas source (9, 10, 10'') has an at least partially open protective-gas storage container (9) in which liquefied protective gas is present that outgases into the protective container (1, 1''),
   characterized in that

   - the protective-gas storage container (9) has a filter element in order to retain bacteria, viruses or other particles present in the liquefied protective gas during outgassing.
2. The device according to Claim 1, characterized in that a heating element (11, 11') is provided for heating the liquefied protective gas present in the protective-gas storage container (9) and for furthering the outgassing of the protective gas.
3. The device according to any one of the preceding Claims, characterized in that the protective container (1) is mobile and has an opening on its bottom in order to introduce the sample into or remove it from the protective container (1) or to place the protective container (1) on the sample.
4. The device according to any one of the preceding Claims, characterized in that

   a) the protective container (1, 1'') has an at least partially transparent container wall in order to make a visual monitoring possible during the handling of the sample, and/or

   b) an outlet opening is arranged on the top of the protective container (1, 1'') for discharging the excess ambient gas.
5. The device according to Claim 4, characterized in that a discharge tube (12, 12'') is connected to the outlet opening on the outside of the protective container (1, 1''), which tube has a downwardly directed mouth located outside of the protective container (1, 1'').
6. The device according to any one of the preceding Claims, characterized in that

   a) the protective container (1, 1'') has at least one gas-tight or gas-exchange-reduced intervention zone (6, 6'') in order to be able to treat the sample in the protective container (1, 1''), and/or

   b) a gas-tight or gas-exchange reduced lock (7, 7'') is provided in order to be able to introduce the sample into the protective container (1, 1'') and remove it out of the protective container (1, 1'').
7. The device according to Claim 6, characterized in that

   a) the lock consists of an opening in the protective container (1'') and of a flexible curtain (14'', 15'') covering the opening, and/or

   b) a lock (14''', 15'') is arranged on each of the opposite sides of the protective container (1'') in order to make an automated operation possible.
8. The device according to any one of the preceding Claims, characterized in that

   a) the protective container (1, 1'') has a thermally insulating container wall in order to prevent condensations caused by cold on its outside, and/or

   b) the protective container (1, 1'') has a heatable container wall in order to prevent condensations caused by cold on its outside, and/or

   c) at least one UV lamp for sterilization is mounted in the protective container (1, 1'').
9. The device according to any one of the preceding Claims, characterized in that

   a) the protective container (1) is substantially bell-shaped or hood-shaped and portable, and/or

   b) the protective container is man-accessible.
10. The device according to Claim 9, characterized by a breathing air supply for an operator in the protective container.
11. The device according to any one of the preceding Claims, characterized in that the protective gas is substantially sterile.
12. A method for handling a sample, in particular, for treating, examining or inserting or extracting a cryosample, the sample being surrounded during the handling by an ambient gas that is cooled, dried and/or at least partially replaced with a protective gas in order to avoid a deterioration of the sample by the ambient gas during the handling of the sample, with the following steps:

    - Introduction of the sample into a protective container (1, 1''),

    - Cooling, drying and/or at least partially replacing the ambient gas present in the protective container (1, 1'') in order to avoid a deterioration of the sample by the ambient gas,

    - The use of a protective gas source (9, 10, 10'') in order to fill the protective container (1, 1'') at least partially with a protective gas that prevents a deterioration of the sample during its handling,

    - wherein liquefied protective gas is outgassed into the protective container (1, 1'') from an at least partially open protective-gas storage container (9) of the protective gas source (9, 10, 10''),
    characterized in that

    - the protective gas is filtered prior to the filling of the protective container (1, 1'') in order to retain bacteria, viruses or other particles.
13. The method according to Claim 12, characterized in that the sample is first arranged in a sample container and is not removed from the sample container until in the protective container.
14. The method according to Claim 13, characterized in that the protective container (1, 1'') is filled at least partially with the protective gas prior to the removal of the sample from the sample container.
15. The method according to any one of Claims 12 to 14, characterized in that

    a) liquefied protective gas is heated in order to further the outgassing of the protective gas, and/or

    b) the protective container (1, 1'') has an opening on its bottom and is placed on the sample container with the sample in it before the sample is removed from the sample container, and/or

    c) the container wall of the protective container (1, 1'') is heated in order to prevent a condensation on the container wall, and/or

    d) the sample in the protective container (1, 1'') is irradiated with UV light for sterilization, and/or

    e) the protective gas is substantially sterile.

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